Certain 2-substituted amino-heterocyclic imine compounds



United States Patent This invention relates to novel heterocyclic amineswhich possess valuable fungicidal properties.

It has been found that heterocyclic amines-of the general Forumla I f-C-HNR A CnHZ L (I) wherein R represents an alkyl with from 8 to 15carbon atoms which may be substituted, or an aralkyl radical which maybe substituted, a substituted aryl, cycloalkyl, heterocyclic radical, orpolyalkylenoxy radical, all radicals being defined more specificallybelow, and n represents a whole number from 3 to 15.

From 3 to not more than 7 of the carbon. atoms of C H are ring membersof ring A.

Their salts, with inorganic and organic acid as well as their quaternarysalts, have excellent fungicidal properties.

Compounds of the general Formula I areobtained by reacting equivalentamounts of a lactirn ether of the formula wherein R represents a loweralkyl radical having 1 to 3 carbon atoms, Q represents oxygen or sulfur,and

' n has the above given meaning,

preferably in the presence of an organic solvent and of a tertiary amineas catalyst, with a primary amine of the general formula NHz-R .(HI)

wherein R has the meaning given above. As organic solvents, e.g.aromatic hydrocarbons, alcohols, esters, ketones, ethers, etc. are used.

Examples of tertiary amines are pyridine, trimethylamine,triethyla'rnine, triethanolamine, etc. In the reaction, the radical QRis split off and an alcohol or mercaptan is formed. By the term saltsare meant salts of inorganic and organic acids as well as the quaternarysalts. The salts of inorganic and organic acids with compounds of thegeneral Formula I are obtained by reacting optionally in thepresence ofneutral organic solvents or of water, the reaction products obtained bythe process described, with'equivalent amounts of an inorganic ororganis acid such as hydrochloric acid, sulfuric acid, phosphoric acid,formic acid, acetic acid, propionic acid, sorbic acid, oxalicacid,.succin ic acid, phthalicacid, p-toluene sulfonic acid, and others.

The quaternary salts are obtained by reacting equivalent amounts ofcompoundsyof the general Formula I with conventional quaternisingagents, e.g. reactive esters of sulfuric acid and toluene sulfonic acid,or reactive derivatives of alcohols, e.g. methyl iodide, butyl bromideor'benzyl. chloride. This reaction may be performed in the presence ofan organic inert solvent e.g. benzene, or

of water.

By the symbol C,,H in the Formulas I and H are meant alkylene radicalswith from 3 to 15 carbon atoms which may be substituted by branched orstraight chain alkyl radicals, but of which from 3 to not more than 7carbon atoms are ring members of ring A.

More specifically, R in Formula I represents alkyl with from 8 to 15carbon atoms, bromoalkyl with from 8 to 15 carbon atoms, chloroalkylwith from 8 to 15 carbon atoms, alkoxy-alkyl having a total of from 4 to20 carbon atoms, alkylthio-alkyl having a total of from 4 to 20 carbonatoms, alkoxy-alkoxy-alkyl with from 5 to 15 carbon atoms, andalkoxy-alkoxy-alkoxy-alkyl with from 7 to 15 carbon atoms, all alkyl andalkoxy portions of the four last-mentioned radicals except the terminalalkoxy or alkylthio portion having at least 2 carbon atoms.

Examples of compounds of the general Formula II are the O-methyl,O-ethyl, O-propyl lactim ethers, the methyl ethers of the 4-tert. butyl,4-amyl, 4-tert. butyl-6-met-hyl and 4,6-diisopropyl caprolactim, as wellas the corresponding thioethers of the lactim forms of a-pyrrolidone,a-piperidone, caprolactam, enanthlactam and capryl lactam.

The following are employed as amines of Formula III: octylamine,decylamine, undecylamine, lau-rylamine, tetra or pentadecylamine,polychlorooctylamine, polychlorolaurylarnine, rnyristylamine,y-methoxypropylamine, 'yethoxypropylamine, ry-(polyethoxy)-propylamineand others.

The compounds of Formula I or their salts are suitable in particular asactive substances for fungicidal agents. 7 Due to their slight toxicityto war-m blooded animals and the absence of phytotoxicity in theconcentrations applied in practice, which vary between 0.1 to 2%calculatedon the active substance, the compounds of Formula I areparticularly suitable for plant protection. The use of the activesubstances as fungicides in orchards is of particular importance. Inaddition the active substances according to the invention can be used asdry seed dressing agents as they have an excellent action, e.g. onTilletia tritici, Fusarium culmorum, etc. and they do not inhibitgermination.

The following examples describe the production of the active substancesaccording to the invention. Parts are given therein as parts by weightunless stated otherwise and the temperatures are in degrees centigrade.

EXAMPLE 1 12.7 parts of O methyl caprolactim 18.5 parts of ndodecylamine, 200 parts by volume of ethanol and 1.0 part oftriethylamine are refluxed for 20 hours. The main amount of the ethanolis then evaporated off in vacuo and the residue is taken up in ether andwashed with water. On evaporating the ether solution, the 7--dodecylamino-3,4,5,6-tetrahydro-2H-azepine obtained is recrystallizedfrom petroleum ether.

On dissolving in the equivalent amount of dilute hydrochloric acid, thehydrochloride is obtained (recrystallized from water or acetone).

In an analogous manner, there are produced from 7-dodecylamino-3,4,5,6-tetrahydro-2H-azepine and the corresponding diluteacid the sulfate, nitrate, phosphate, formiate, acetate, propionate,sorbate, oxalate, succinate, fumarate, 'phthalate, p-toluenesulfonateand benzoate of 7-dodecylamino-3,4,5,6-tetrahydro-2H-azepine.

EXAMPLE 2 14.3 parts of Z-methylthio-3,4,5,6-tetra.hydro-2H-azepine, 200parts of volume of benzene, 18.6 parts of laurylamine and l-part oftriethylamine are refluxed for 20 hours. The solution is concentrated invacuo and the O-methyl caprolactim produced as described in OrganicSynthesis '31, 72 (1951).

residue is recrystallised from petroleum ether; the 7-1aurylamino-3,4,5,6-tetrahydro-ZH-azepine is then converted to thehydrochloride according to Example 1.

7 parts of 7-laurylamino-3,4,5,6-tetrahydro-2H-azepine are dissolved in100 parts by volume of anhydrous benzene, and 3.25 parts ofdimethylsulfate are added drop by drop and the resulting mixture is thenrefluxed for one hour. On evaporating the benzene the quaternary 7-laurylainino 3,4,5,6-tetrahydro-2H azepine dimethylsulfate is obtainedas water-soluble viscous oil which decomposes upon distillation.

Further compounds of Formula I of which the data for n, z, whichrepresents the number of carbon atoms being ring members'in ring A, thealkyl branching at ring A, if present, as well as R, are given in theTable I below, and salts and quaternary salts of these compounds, ofwhich the anion or quaternizing agent is also given below, are producedin the manner described in Examples 1 and 2 from equivalent amounts ofthe corresponding lactim ether of Formula II and the corresponding amineof Formula III.

The starting materials are either known or have been produced in amanner analogous to that of making the known starting materials.

The compounds of structure I are suitable as active substances infungicidal agents for the most various forms of application such asinhibition and repression of the growth of fungi on plants and partsthereof as Well as the protection of organic materials of all types suchas wood, textiles, furs, leather, paper, synthetic substances, etc. fromattack and decomposition by fungi. For these purposes the activesubstances are employed in a finely distributed form as such or combinedwith suitable carriers and distributing agents. They can also be used incombination with other fungicidally active substances as well as withfungistatica and bacteriostatica. To increase the range of action, alsoinsecticidally or nematocidally active substances, etc. can be added tothe active substances used according to the invention.

To produce fungicidal agents according to the invention the activesubstances can be mixed, for example, with solid, pulverulent carrierssuch as e.g. talcum, kaolin, loess, chalk or ground limestone. Ifdesired, the pulverulent agents obtained can be made suspendable inWater by the addition of suitable wetting and-dispersing agents such assulphite waste liquor. In addition, the active substances as such insolid, finely ground form, can be suspended in water with the aid ofcapillary Table l Alkyl branching Salt COCO

n-Dodecyl n-Octyl n-Deoyl 8-Methyl-nonyl n-Tetradecyl formula 051112.45C14 .5.

CzHs-O-CHg-CHrOCH2-OH2OC3Hg 8-ehloro-octyl 5-bromo-pentyl Mixture of perchlorooctyl radicals of the Chloride.

average 4-t-butyl n-OetyL 4-t-butyln-Decyl 4-1;butyl n-Dodecy 4-t-butyln-Tetradecy n-Deeyl 10 n-Dodecyl 10 n-Tetradeeyl 10 n-Dodecy1 13n-Dodeeyl. 15 n-Dodeeyl- 7 n-Oetyl. 7 n-Decy 7 n-Dodecyl 7 n-Tetradecyl5 n-OctyL Quaternized as described in Example 2 with diethyl sulfate. 335 5 n-Dodeeyl Dimethyl sulfate. 34--.. 5 5 n-Dodecyl--- n-Butyl bromide.

EXAMPLES 35-36 active substances, or they can be emulsified in water,after dissolving them in organic solvents, with the aid of suitableemulsifying agents. Also, the active substances can be dissolved inorganic solvents, e.g. in chlorinated hydrocarbons such astrichloroethylene, or in medium petroleum fractions, boiling range 100to 200 possibly with the addition of auxiliary solvents such as acetoneor higher ketones, e.g. cyclohexanone. Finally, the active substancescan also be employed in the form of aerosols, smoke or mist,particularly in storerooms and greenhouses.

The fungicidal active substances are applied to an organic material tobe protected generally either by ad- ,mixture therewith, by spraying orby impregnating with organic-aqueous or aqueous solutions of the activesubstance which can contain the active substance in dispersion orsuspension.

5 The following examples further illustrate the production of somefungicidal agents:

EXAMPLE I 6 I claim: 1. A member selected from the group consisting of(a) a compound of the formula i 5 CNHR 20 parts of 4-tert.butyl-7-myristylamino-3,4,5,6-tetra- (A) hydro-'lH-azepine produced asdescribed in Example 20 are finely milled in a ball mill with 4 parts ofa polyvinyl N (I) pyrrolidone dispersing agent and 76 parts of Water.The paste so obtained is suspended in water and is used for and thecombatting of fungi, particularly in orchards. 10 (b) a fungicidallyeffective salt of the compound of Formula I and an acid; EXAMPLE II R inFormula I being a member selected from the group consisting of alkylwith from 8 to 15 carbon 50 parts of7-n-octylamino-3,4,5,6-tetrahydro-2H-aze- 1 atoms, aikoxy aikyi with atotal of from 4 to 2 pine, produced as in Example 7, 2 parts of anadhesive carbon atoms 1 1 i 1 with a .totai f f having a polyvinylalcohol base, parts of sulphite waste 4 to 20 carbon atoms,aikoxwaikoxyhhqi with a liquor, 16 Parts of champagne chalk, 20 Parts ofkaohn v total of from 5 to carbon atoms, alkoxy-alkoxyand 2 parts of awetting agent having an alkyl and aryl alkoxy-alkyl with a total of from7 to 15 carbon Sulphonate base are milled together, mixed, and againatoms, all alkyl and alkoxy portions except the termi- A wettable POWdTIS obtained C3D nal alkoxy and alkylthio groups of the last men besusPended in f and is suitable in Particular for tioned four membershaving at least 2 carbon atoms, 1156 in fruit Cultivatlonchloroalkylwith from 8 to 15 carbon atoms, and

n being an integer ranging from 3 to 15, from 3 to not EXAMPLE In morethan 7 of the carbon atoms of grouping C H 10 parts9-n-dodeeylamhno-3,4,5,6,7,8-hexahydro-2H- 2 ii g ffg i azonine,produced as described in Example 26, are dis- Compoun o 6 0mm a solvedin 15 parts of dimethyl sulphoxides and 65 parts of cyclohexanone. 10parts of an alkylaryl polyethylene C NH OHHZB oxide (ratio 1:10) aremixed into this solution until II homogeneity is attained. An:emul-sifiable solution is N obtained which can be diluted to anyconcentration de- Slred' EXAMPLE IV 3. A compound of the formula Thefungicidal activity of the compounds of general Fonmula I was determinedby the germination test with ((3 H933 spores of the following types offungi: Alfernaria tenu is, N Botrytis cinerea, Clasterosparium c.,Coniothyrium dipl., Fusarium culm., Mucor spec., Penicillium spec., and40 Swmphyh-um 6mm 4. A quaternary compound of the formula A determinedamount of a 1%, 0.1% and 0.01% solution of active substances in acetonewas placed, all under equal conditions, in four petri dishes ofidentical size. a fi* The solvent was evaporated whereupon a levelcoating N of active substance ready for inoculation was obtained, ineach of the four dishes. After inoculation, the dishes were kept for 168hours at 20 C. in an atmosphere of Dlmethylsulfate 80% humidity. Thegerminated spores were then counted. The following table shows thevalues at which A compound of the formula at least a 90% inhibition ofgermination was attained. The value in the table represents at least a90% C-NHC12Hz inhibition of germination attained by the residue of onecc. of the aforesaid 1% solution of active substance in acetone (:137active substance per sq. cm.) represents the same effect attained by theresidue of one cc. 6 A compound f the f l of the aforesaid 0.1%solution, and the same effect attained with the residue of one cc. of0.01% solution of active substance. 0 means no noticeable inhibi- NHSH11 tion of germination when using the aforesaid 0.1% solu- Q; tion.

Alt. Botr. Clast. Com. Fus. Muc. Pen. Stem. ten. cin. c. dipl. calm.spec. spec. cons.

7-methylamino-A -azacycloheptene 0 0 0 O 0 O 0 0 Cetelin e192i'.),Collection Czechoslov. Chem. Commun.

fiffidodecylamino-A -azacycloheptene (Example 1) Quaternary7-n-octylaminoA -azacycloheptene-dimeth- I yl lfa (Ex mple 33) 7 7. Acompound of the formula 8 References Cited by the Examiner Ge'hrke:Faserforsch. Textiltech, v01. 13, page 95 (1962).

5 NICHOLAS S. RIZZO, Primary Examiner.

JOHN D. RANDOLPH, Examiner.

1. A MEMBER SELECTED FROM THE GROUP CONSISTING OF (A) A COMPOUND OF THEFORMULA